Stable Pyrrole-Linked Bioconjugates through Tetrazine-Triggered Azanorbornadiene Fragmentation.
Hoyt, Emily A
Lopes Bernardes, Goncalo
Angewandte Chemie (International ed. in English)
MetadataShow full item record
Gil de Montes, E., Istrate, A., Navo, C. D., Jiménez-Moreno, E., Hoyt, E. A., Corzana, F., Robina, I., et al. (2020). Stable Pyrrole-Linked Bioconjugates through Tetrazine-Triggered Azanorbornadiene Fragmentation.. Angewandte Chemie (International ed. in English), 59 (15), 6196-6200. https://doi.org/10.1002/anie.201914529
We have developed an azanorbornadiene bromovinyl sulfone reagent that allows cysteine-selective bioconjugation. Subsequent reaction with dipyridyl tetrazine led to bond-cleavage and formation of a pyrrole-linked conjugate. The latter involves ligation of the tetrazine to the azanorbornadiene-tagged protein through inverse electron demand Diels–Alder cycloaddition with subsequent double retro-Diels–Alder reactions to form a stable pyrrole linkage. The sequence of site-selective bioconjugation followed by bioorthogonal bond-cleavage was efficiently employed for the labelling of three different proteins. This method benefits from easy preparation of these reagents, selectivity for cysteine, and stability after reaction with a commercial tetrazine, which lends it to the routine preparation of protein conjugates for chemical biology studies.
Aza Compounds, Norbornanes, Cysteine, Pyrroles, Cycloaddition Reaction
European Commission Horizon 2020 (H2020) ERC (676832)
Royal Society (URF\R\180019)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (701473)
External DOI: https://doi.org/10.1002/anie.201914529
This record's URL: https://www.repository.cam.ac.uk/handle/1810/301534
All rights reserved